Doi:10.1016/j.metabol.2004.12.010

Metabolism Clinical and Experimental 54 (2005) 657 – 668
Cortitrol supplementation reduces serum cortisol
William J. KraemerT, Duncan N. French, Barry A. Spiering, Jeff S. Volek,
Matthew J. Sharman, Nicholas A. Ratamess, Daniel A. Judelson,
Ricardo Silvestre, Greig Watson, Ana Go´mez, Carl M. Maresh
Human Performance Laboratory, Department of Kinesiology and
Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT 06269, USA
Received 9 August 2004; accepted 14 December 2004
The supplement Cortitrol was formulated to mitigate the cortisol response to physiological and psychological stress. Therefore, the
purpose of this study was to examine the effects of Cortitrol on serum cortisol concentrations before, during, and after a high-intensityresistance exercise protocol (EX) and a resting control day (REST). We used a matched, balanced, randomized, double-blind, placebo-controlled, cross-over design. Blood samples were obtained at matching time points during EX and REST. Cortitrol significantly ( P b .05)reduced cortisol area under the curve concentrations during REST. During EX, Cortitrol reduced cortisol concentrations at 20, 10, and 0minutes pre-exercise, at mid-exercise, immediately post-exercise, and at 5 minutes post-exercise. In addition, serum cortisol and plasmaadrenocorticotropin hormone area under the curve concentrations during EX were significantly lower after Cortitrol than placebo.Furthermore, Cortitrol significantly reduced free radical production. This was indicated by significantly lower plasma malondialdehydeconcentrations at the 65-minute post-exercise time point during REST, and at pre-exercise, immediate post-exercise, and 65 minutes post-exercise during EX. Serum total testosterone, free testosterone, dehydroepiandrosterone, and growth hormone showed exercise-inducedincreases but no treatment effects. These data demonstrate that Cortitrol was effective in modulating the physiological stress responses ofexercise from the anticipatory rises before physical stress and into early recovery by reducing cortisol and associated free radical production.D 2005 Elsevier Inc. All rights reserved.
physical training, labor in the work place, or chronicphysiological stress.
When human beings are confronted with physiological
There are 2 components of the supplement regimen
and/or psychological stress the adrenal gland secretes
tested. The first component is a general vitamin/mineral
cortisol. This response increases glucose and fatty acid
combination of pantothenic acid (30 mg), pyridoxine
concentrations in the blood and stimulates gluconeogenesis
(10 mg), riboflavin (8.5 mg), thiamine (7.5 mg), vitamin
to prepare the body for bfight or flight.Q Although cortisol is
C (250 mg), calcium (100 mg), and magnesium (100 mg).
necessary for normal physiological function, chronic ele-
B vitamins (pantothenic acid, pyridoxine, riboflavin, and
vations have a negative impact on muscle and immune cell
thiamine) were added to prevent deficiencies common in
function and bone metabolism. Nutritional interventions
active individuals which have been shown to decrease
aimed at partially attenuating the cortisol response would
prove valuable for those faced with, for example, intense
2max, onset of blood lactate accumulation, peak power,
and mean power Vitamin C supplementation has thepotential to reduce blood pressure, cortisol, and subjectiveresponses to acute psychological stress in healthy subjectsas well as exercise stress responses in competitive
T Corresponding author. Human Performance Laboratory, Department
weightlifters Calcium intake is essential for minimizing
of Kinesiology, University of Connecticut, Storrs, CT 06269-1110, USA.Tel.: +1 860 486 6892; fax: +1 860 486 6898.
bone loss and osteoporosis a disease common among
E-mail address: william.kraemer@uconn.edu (W.J. Kraemer).
individuals with persistently elevated cortisol levels
0026-0495/$ – see front matter D 2005 Elsevier Inc. All rights reserved.doi:10.1016/j.metabol.2004.12.010
W.J. Kraemer et al. / Metabolism Clinical and Experimental 54 (2005) 657 – 668
Finally, chronic stress may exacerbate preexisting magne-
marathon had a decreased inflammatory response, cortisol/
sium deficiencies, which can lead to impaired ergy
dehydroepiandrosterone (DHEA) ratio, and imm
metabolism and decreased physical work capacity [7].
pression during the postmarathon recovery period [16].
The second component of the supplement is Cortitrol, a
Although cortisol is necessary to respond to physiological
proprietary herbal anticortisol blend containing magnolia
stress, chronic elevation of cortisol may have negative effects
bark extract (Magnolia officialis), l-theanine (from Camillia
on a host of target tissues, such as reduced immune cell
sinensis), Epimedium extract (Epimedium koreanum),
function, protein wasting in muscle, and suboptimal bone
phophatidylserine (soy derived), and b-sitosterol. Limited
metabolism. However, complete elimination of the overt
data exist on the effectiveness of these herbal supplements;
cortisol response to stress would be physiologically inap-
however, preliminary studies show promising results.
propriate for normal human health. Thus, Cortitrol was
Magnolol, a phenolic constituent of magnolia bark, has
designed and formulated to reduce the magnitude of the
been shown to suppress cortical serotonin (5-hydroxytryp-
overt stress response and absolute cortisol concentrations.
tamine) release , which may be advantageous because
Intense resistance exercise and training has been shown to
serotonin plays a role in stress and anxiety–related disorders
cause dramatic increases in cortisol levels Further-
l-theanine, commonly found in tea, may prime blood
more, athletes show elevated cortisol levels in anticipation of
T cells and provide natural resistance to infection and
intense physical challenge Therefore, high-intensity
promote brain a-wave and suppress b-wave activity
resistance exercise provides an ideal forum to test the
Epimedium has been shown to lower cortisol levels in
purported benefits of Cortitrol. The purpose of this investi-
animal models Monteleone et al showed that
gation was to determine the efficacy of Cortitrol to influence
phosphatidylserine supplementation attenuated the cortisol
cortisol responses to an intense physical exercise stress
response to physical stress in healthy men. Finally, subjects
model in human beings known to dramatically increase
supplementing with b-sitosterol before competing in a
cortisol concentrations in the blood. We hypothesized that
A. =======================================================================
Blood Sample Diet Records
===============================================
4 x Squat 4 x Bench4 x Row 4 x PressBlood Sample DEXA
Fig. 1. A, Experimental design. A balanced, randomized, double-blind, placebo-controlled, cross-over design was used to determine the effects of Cortitrol. Cindicates control day; E, exercise day. B, Testing sequence during exercise testing days. Blood samples were obtained at matching time points during restingcontrol days. DEXA indicates dual-energy x-ray absorptiometry.
W.J. Kraemer et al. / Metabolism Clinical and Experimental 54 (2005) 657 – 668
supplementation would result in decreased cortisol concen-
only 10 repetitions to be performed but both experimental
trations before, during, and after the exercise challenge.
workouts used very similar if not identical resistances in theworkout sequences because of arization andpractices of the experimental protocol [18,21]. To maximally
stimulate all major muscle groups, the back squat, bench
press, bent over row, and shoulder press exercises were used.Two minutes of rest was allowed between each set and
The Institutional Review Board for use of Human
exercise. This protocol has been found to produce high phys-
Subjects in Research at the University of Connecticut
iological stress, as evidenced by cortisol 00 nmol/L)
approved all study procedures before its initiation. Twenty-
and lactate concentrations ( N14 mmol/L) Blood was
one men volunteered to participate and gave written
collected at 30 minutes (À30), 20 minutes (À20), and 10
consent after being informed of the risks associated with
minutes (À10) pre-exercise, immediately before exercise
the study. All subjects acted as their own controls with the
(PRE), at the midpoint of the exercise protocol (MID),
within-group design used in this study. Subjects were
immediately post-exercise (IP), and at 5 minutes (+5), 10
healthy, college-aged men with resistance training experi-
minutes (+10), 15 minutes (+15), 25 minutes (+25), 35
ence of 4 years or more. Mean (FSD) age and height were
minutes (+35), 45 minutes (+45), 55 minutes (+55), and 65
21.1 F 1.2 years and 180.5 F 7.0 cm, respectively. Each
minutes (+65) after exercise. Testing procedures for REST
subject was specifically instructed to maintain their indi-
(including duration, timing and number of blood draws, and
vidual exercise routine (frequency, duration, and intensity)
time of day) were identical. All treatment sessions were
during the study, which was verified through evaluation of
performed within the same identical time of day window
physical activity diaries. Each subject was tested for
(8:00 to 10:30 am) to reduce the influence of normal
individual 1 repetition maximum (RM) using previously
circadian variations, which can add to experimental variance.
described methods One RM of the back squat, bench
After completion of EX and REST protocols, subjects were
press, bent over row, and shoulder press exercises were
crossed-over (into either the treatment or placebo group) and
130.8 F 27.4, 112.9 F 21.2, 90.2 F 17.5, and 72.1 F 11.3
Whole body composition was assessed using fan-beam
A matched, balanced, randomized, double-blind, place-
dual-energy x-ray absorptiometry (Prodigy, Lunar Corpo-
bo-controlled, cross-over design was used to determine the
ration, Madison, Wis). Subjects were positioned on the
effects of Cortitrol on serum cortisol concentrations (see
dual-energy x-ray absorptiometry according to the manu-
Subjects were matched according to age, body size,
facturer’s guidelines having removed all metallic objects
and training experience. All subjects used physical activity
from their body. Whole body analysis of fat tissue, lean
diaries and food diaries to replicate lifestyle patterns for the
tissue, and bone mineral content was assessed according to
3 days before each testing protocol. All subjects participated
anatomical landmarks by the same technician using
in several familiarization sessions before exercise testing to
computer algorithms (enCORE version 6.00.270). Coeffi-
reduce the experimental variance from learning effects and
cients of variation for lean body mass and fat mass on
to expose subjects to the physical challenge of the protocol.
repeat scans with repositioning within a group of male
Resting baseline measures were obtained before (V-1) and
subjects in our laboratory were 0.4% and 1.4%, respective-
after (V-2) 1 week of supplementation following the placebo
ly. The same experienced technician performed all measure-
and Cortitrol conditions to determine measurement stability
ments throughout the study period. Body mass was
of the dependent variables. Subjects were then asked to report
measured to the nearest 0.01 kg using an electronic
to the laboratory on 2 separate occasions for each condition:
scale (American Business Equipment Company, Inc, New
once for a resistance training exercise challenge (EX) and
Holland, Pa). Scans were performed on all subjects at 4 time
once for a resting control day (REST). Treatment order wasbalanced and randomized; REST proceeded EX by 48 hours.
The EX protocol consisted of 4 sets of 10 RM using 4
Pre- and post-supplementation body composition and bone characteristics
different exercises. A 10RM (the amount of weight that
allowed only 10 repetitions to be performed) was determined
during familiarization sessions and the resistances used for
each set of every exercise were established with ICC R’s of
more than 0.98 for 2 consecutive exercise sessions. The goal
of the familiarizations was to create a reliable workout that
could be highly replicated to produce a similar if not
identical physiological stress response During the
experimental workout, resistances were reduced to allow
W.J. Kraemer et al. / Metabolism Clinical and Experimental 54 (2005) 657 – 668
points during the study: immediately before and on the
similar foods for 3 days before the exercise bout for each
seventh day of the supplementation protocol for both the
phase. A registered dietician and associated staff counseled
placebo and treatment conditions. No significant changes in
and supervised the subjects to ensure no nutritional
body compoobserved during the course of the
variation would confound the dependent variables. To
assist participants in duplicating their diet during phase 1and 2, subjects completed detailed 3-day diet diary records
during both periods. Copies were made of phase 1 diet
To possible confounding effects of diet on
records and returned to subjects during phase 2 to enhance
cortisol [22,23], subjects were instructed to consume
reproducibility. Food diaries were analyzed for energy and
Resting ControlCortitrol Exercise ProtocolCortitrol
Fig. 2. A, Cortisol concentrations during the resting control day. *P b .05, significantly greater than corresponding Cortitrol value. #P b .05, significantlylower than corresponding Cortitrol value. Data are expressed as mean F SE. Insert, Area under the curve comparison for resting day. *P b .05 fromcorresponding placebo condition. B, Cortisol concentrations during the exercise challenge day. *P b .05, significantly different than corresponding placebovalue. Data are expressed as mean F SE. Insert, Area under the curve comparison for exercise challenge day. *P b .05 from corresponding placebo condition.
W.J. Kraemer et al. / Metabolism Clinical and Experimental 54 (2005) 657 – 668
Resting ControlCortitrol ACTH (pmol Exercise ProtocolCortitrol ACTH (pmol
Fig. 3. A, Corticotropin concentrations during the resting control day. *P b .05 from corresponding placebo condition. B, Corticotropin concentrations duringthe exercise challenge day. *P b .05 from corresponding placebo condition. #P b .05 from corresponding pre-exercise time point. Data are expressed asmean F SE.
macro/micronutrient content with NUTRITIONIST PRO
samples were assayed in duplicate and were decoded only
(version 1.3, First Databank Inc, The Hearst Corporation,
after analyses were completed (ie, blinded analysis proce-
dure). For all procedures, samples were thawed only oncebefore analysis. The minimum detection limits for cortisol,
total and free testosterone, DHEA, and corticotropin were
Serum concentrations of cortisol, total and free testos-
2.76 nmol/L, 0.14 nmol/L, 0.66 nmol/L, 0.346 nmol/L and
terone, and DHEA were determined in duplicate using
0.264 pmol/L, respectively. In all cases, intra-assay and
commercially available enzyme immunoassay kits (Diag-
nostic Systems Laboratories, Webster, Tex) according to the
Plasma growth hormone (GH) concentrations were
manufacturer’s procedures. Plasma corticotropin concentra-
determined in duplicate using an 125I liquid-phase immu-
tions were determined using enzyme-linked immunosorbent
noradiometric assay (Nichols Institute Diagnostics, San
assay (Diagnostic Systems Laboratories, Webster, Tex). All
Juan, Capistrano, Calif). This commercially available
W.J. Kraemer et al. / Metabolism Clinical and Experimental 54 (2005) 657 – 668
immunoradiometric assay uses 2 monoclonal antibodies of
previously described [24,25] Briefly, 50 lL of unknown
high affinity and specificity for GH, each detecting a
sample and MDA standard (0.61-19.44 lmol/L; 1,1,2,2-
different epitope on the GH molecule. One of the antibodies
tetraethoxypropane standards) were pipetted into polypro-
was labeled for detection, whereas the other was coupled to
pylene test tubes. Then they were combined with 0.75 mL
biotin. The sensitivity for this assay using the Bo (2 SD)
of 0.44 mol/L phosphoric acid stock solution and 0.25 mL
method was 0.04 ng/mL. Intra-assay variances for GH
of 42 mmol/L thiobarbituric acid (0.6 g of 4,6-dihydroxy-
thiopyrimidine in 100 mL of dH2O). Samples were further
Plasma malondialdehyde (MDA) concentrations were
diluted using 0.45 mL dH2O. All test tubes were then
determined using a thiobarbituric acid assay procedure as
capped, sealed tight, and placed in a preheated water bath at
Resting ControlCortitrol MDA (mmol Exercise ProtocolCortitrol MDA (mmol
Fig. 4. A, Plasma MDA concentrations during the resting control day at the time points corresponding to pre-exercise (Pre), immediately post-exercise (IP), and65 minutes post-exercise (65). *P b .05 from corresponding placebo condition. B, MDA responses during the exercise challenge day. *P b .05 fromcorresponding Cortitrol condition; #P b .05 from the corresponding treatment’s pre-exercise value; ^P b .05 from plasma MDA concentrations resting daycontrol values. Data are expressed as mean F SE.
W.J. Kraemer et al. / Metabolism Clinical and Experimental 54 (2005) 657 – 668
1008C for 60 minutes. After heating, samples were removed
(21% F 2% and 23% F 5%). This minimized the impact of
from the water bath and immediately placed into an ice
dietary variation on endocrine responses between the 2
water bath (08C) until analysis. Samples remained on ice for
treatment conditions. The dietary records of all participants
no longer than 30 minutes before analysis; 1.5 mL of Me-
revealed that they had normal eating patterns; no fad diets
NaOH stock solution was then added to all boiled samples
and/or signs or eating disorders were revealed.
and standards. All tubes were recapped, vortexed, and
There were no pre-supplementation differences between
centrifuged at 3500 rpm for 5 minutes to sediment the
conditions in serum cortisol concentrations (placebo:
precipitated plasma proteins. Plasma concentrations of
F 22.94 nmol/L; Cortitrol: 440.2 F 142.3 nmol/L).
MDA were determined in duplicate. One-millimeter extract
Fig. 2A shows pairwise differences between placebo and
of protein-free plasma was removed from each test tube
Cortitrol at À30, À10, IP, +35, and +55 during REST. The
without disturbing the sedimented precipitate. All samples
insert of demonstrates that cortisol AUC concen-
and standards were transferred to 1.5-mL cuvettes and the
trations during REST were significantly lower for the
absorbance was read at 532 nm using a spectrophotometer
Cortitrol supplementation condition.
(Spectronic 401, Spectronic Instruments Inc, Rochester,NY). To eliminate inter-assay variance, all samples for thisassay were analyzed in the same assay run. In all cases,
Table 2Values for plasma glucose and lactate during resting control and
intra-assay variances were less than 10%.
Plasma glucose and lactate concentrations were deter-
mined using an automated glucose/lactate analyzer (2300
Stat glucose/l-lactate analyzer, YSI, Inc, Yellow Springs,Ohio). Hemoglobin was analyzed in triplicate from whole
blood using the cyanmethemoglobin method (Sigma Diag-
nostics, St Louis, Mo); hematocrit was analyzed in triplicate
from whole blood via microcentrifugation and microcapil-
lary technique. Plasma volume shifts after the workout were
calculated using the formula of Dill and Costill
Paired-sample t tests were used to examine differences
between the 2 days of baseline resting values. Area under
the curve (AUC) analyses were completed using standard
trapezoidal statistical methods. Two-way analysis of vari-
ance with repeated measures was used to examine pairwise
differences in hormonal concentrations and a 2-way analysis
of variance (2 groups Â 2 conditions) was used to evaluate
the AUC data. Appropriate post hoc tests (ie, Fisher LSD or
Tukey tests) were used when a significant F score resulted.
All linear assumptions were tested and, when appropriate,log10 transformations were used and the data were
reanalyzed. Using nQuery Advisor software (Statistical
Solutions, Saugus, Mass), the statistical power for the n
size used ranged from 0.80 to 0.90. Significance in this
There was no significant plasma volume shift pre- to
post-exercise for either condition (placebo: +0.56% F
5.51% placebo; Cortitrol: +4.12% F 7.26%, P N .05). This
was likely because of ad libitum water intake during the rest
There were no significant differences between Cortitrol
and placebo supplementation, respectively, for dietary
energy (9517 F 3756 and 10752 F 4246 kJ), and the
percent energy from carbohydrate (48% F 8% and 43% F
a P b .05 from corresponding resting control day time point.
13%), fat (31% F 9% and 34% F 12%), and protein
b P b .05 from corresponding pre-exercise value.
W.J. Kraemer et al. / Metabolism Clinical and Experimental 54 (2005) 657 – 668
Table 3Values for total testosterone, free testosterone, and DHEA during resting control and exercise days
a P b .05 from corresponding Cortitrol condition.
b P b .05 from corresponding resting control day time point.
c P b .05 from corresponding pre-exercise value.
During EX, subjects had significantly lower cortisol
AUC between the 2 conditions (placebo: 127.6 F 69.7
concentrations after Cortitrol supplementation than placebo
pmol/L; Cortitrol: 131.7 F 73.3 pmol/L). Corticotropin
at À20, À10, PRE, MID, IP, and +5 (Furthermore,
responses to EX are presented in As expected,
total exposure to absolute molar concentrations of cortisol,
plasma corticotropin significantly increased in response to
as demonstrated by AUC analysis, was significantly lower
EX and concentrations were elevated above PRE values
during the Cortitrol phase of the trial than the placebo phase
through +55. Cortitrol treatment conditions were lower than
(insert). There was a significant increase in cortisol
placebo at +5 and +10. Corticotropin was significantly
greater during EX than during REST. Corticotropin AUC
Corticotropin responses are presented in There
was significantly lower for Cortitrol than placebo (placebo:
were no significant differences between the resting baseline
233.1.6 F 142.9 pmol/L; Cortitrol: 209.0 F 117.2 pmol/L).
measures. In general, there were no significant differences
shows the MDA responses during the REST.
between REST values, although a significant difference was
Significant differences were noted at +65. presents
found at À20 (see No differences were observed in
MDA data for EX. MDA values at PRE, IP, and +65 for
W.J. Kraemer et al. / Metabolism Clinical and Experimental 54 (2005) 657 – 668
Cortitrol were significantly lower than placebo. Cortitrol
Androgen concentration values are shown in Table 3.
values were significantly lower during EX than REST.
Total testosterone, free testosterone, and DHEA all followed
There was an exercise-induced increase in MDA for both
a similar response pattern. No differences between the 2
baseline days (V-1 and V-2) or during REST were apparent.
Table 2 presents the metabolic profile of plasma glucose
During EX, no significant differences between conditions
and lactate. No significant changes were noted in either
were observed over the pre-exercise time frame. Significant
variable during the baseline days (V-1 and V-2) or REST. As
exercise-induced increases were observed from MID to +35
expected, plasma glucose and lactate were significantly
in both conditions. All post-exercise values were signifi-
elevated above PRE values post-exercise. Glucose values
cantly higher than corresponding REST values. Placebo
did not return to PRE values until +45; lactate values
DHEA values were significantly lower than Cortitrol values
remained significantly elevated above PRE values through
+65. Plasma glucose values for EX were significantly higher
than corresponding REST values from MID to +45. Plasma
significant differences were observed over the baseline days
lactate values for EX were significantly higher than
or during REST for either condition. There were significant
corresponding REST values from MID to +65.
exercise-induced increases in GH during EX compared toREST. During EX, there were significant pre- to post-exercise increases in GH concentration.
Table 4Mean (FSD) values for GH during resting control and exercise days
It should be clear that the primary purpose of this study
was to examine the ability of Cortitrol to modulate cortisol
concentrations resulting from performance of a resistance
exercise physical stress model. How any reductions in
cortisol would impact physiological adaptations in various
target tissue (eg, muscle and cell) cannot be determined with
this experimental design and requires further experimenta-
tion. Thus, we wanted to know if Cortitrol could influence
the stress response. We know that cortisol plays important
regulatory roles in various physiological functions and
complete elimination of the catabolic response would not
be optimal in homeostatic regulation. It is also important to
understand that elimination of the cortisol response to
physical stress would not be optimal to physiological
adaptations. However, positive changes in muscle size
development have occurred with reductions of cortisol over
the first 8 weeks of resistance training Nevertheless,
when cortisol is produced in excess, receptors beyond the
primary targets are exposed to higher than normal molar
concentrations of cortisol producing effects that may in fact
be counterproductive to optimal tissue repair and remodeling
(eg, reductions in immune cell activation in the attempt to
conserve glycogen breakdown in the muscle yet inhibit
repair with limited B-T-cell function and macrophage
abilities to clean up degraded proteins in muscle). It is the
chronic elevations of cortisol beyond normal concentrations
that are most concerning to optimal physiological function
and can have a negative impact on many target tissues
including muscle, bone, and immune cells. We wanted to
create an acute stress response with high concentrations of
cortisol using our bstress modelQ of high-intensity resistance
exercise to determine the influence of Cortitrol supplemen-
tation on the cortisol response. This was done to determine
the impact of the dietary supplement on a known physio-
logical stress response of exercise to gain data on its
P b .05 from corresponding resting control day time point.
b P b .05 from corresponding pre-exercise and baseline values.
physiological efficacy but its role in adaptive responses
W.J. Kraemer et al. / Metabolism Clinical and Experimental 54 (2005) 657 – 668
cannot be determined from this experimental design. Data
exposure measure. Reduced corticotropin AUC for Cortitrol
from this investigation show that Cortitrol plays an important
indicated subtle alterations of the tropic hormone signal
modulatory role in dramatically reducing cortisol release
during EX. These data are consistent with a lower
before, and immediately after intense resistance
hypothalamic-pituitary signal for cortisol production, sup-
exercise (Fig. 2). Furthermore, the accumulated reduction in
porting a mechanism related to the second component of
cortisol over the 95-minute block of time on both the REST
Cortitrol: the proprietary herbal combination containing
and EX days suggests that Cortitrol reduces the total tissue
magnolia bark, l-theanine, Epimedium, phosphatidylserine,
exposure to cortisol. A reduction in free radical formation, as
and b-sitosterol. In particular, phosphatidylserine may have
measured by plasma MDA values, was also observed
between the treatment conditions during EX. Thus, this
Monteleone et al showed that, in addition to
study gives initial insight into the influence of Cortitrol as a
reduced cortisol concentrations, phosphatidylserine supple-
general modulator of the adrenal stress response.
mentation attenuated the corticotropin response to physical
The findings of this study should be viewed as the effects
stress in healthy men. Our data indicate that part of the
of a composite supplementation formula consisting of
cortisol stress response, which was altered by the Cortitrol
various nutritional attributes, which together, work to reduce
treatment, was mediated by subtle changes in the secretion
physiological stress. This formulation consists of a general
of the regulatory hormone corticotropin.
vitamin/mineral complex and a proprietary blend of herbal
Of particular interest was the differential responses of the
compounds with known anticortisol effects
Cortitrol and placebo treatments with regard to oxygen
Both components may be necessary to mediate the observed
reactive species formation, as measured by MDA concen-
trations (see Fig. 4). This is a novel and unique finding that
A dearth of information exists as to the role of nutritional
may have dramatic ramifications because free radical
supplementation to impact stress responses of cortisol.
production after exercise is known to produce chemical
Vitamin C has been implicated in reducing cortisol
damage to various target tissues. Although speculative, the
responses to physical exercise In prior work using
significant reduction in MDA could be due to one or more
resistance exercise, Marsit et al showed a subtle
of the antioxidant components of Cortitrol. One of the
reduction in cortisol after supplementation with 1000 mg
naturally occurring bioactive derivatives identified in
vitamin C 24 hours before exercise. The treatment regimen
magnolia officialis is the biphenolic compound magnolol,
used in the present study provided 250 mg of vitamin C,
which has been shown to be a potent antioxidant
suggesting that ascorbic acid may have been a partial
b-Sitosterol has also been shown to have antioxidant
contributor to the positive effects observed in resting
properties that protect against lipid peroxidation Some
cortisol concentrations. In addition, magnolia bark extract,
studies also show vitamin C increases serum oxygen-radical
because of its antioxidant capacity and phosphatidyl-
absorbance capacity Thompson et al specifi-
serine, because of its effects on neuroendocrine responses to
cally reported a reduction in plasma MDA during recovery
exercise may have also contributed to the reduction
from exercise after vitamin C supplementation. The precise
role of cortisol in mediating the reduction in MDA remains
It is interesting to note that Cortitrol attenuated the
unclear. It is plausible that these other antioxidant com-
cortisol response exclusively during the pre-exercise and
pounds worked alone or in concert to reduce MDA
early recovery period during EX, whereas no differences
independent of any effect on circulating cortisol. Alterna-
were apparent from +10 to +65. Subjects typically display
tively, there is some indication that elevated cortisol
an anticipatory rise in cortisol before exercise because of
increases lipid peroxidation and thus the decrease in
psychological fear of intense physical challenge
cortisol would be associated with lower MDA levels. This
Inherent to this model was the use of formal practice of
finding implicates the role of Cortitrol in tissue repair and
the exercise challenge to specifically familiarize each
recovery, as well as in adrenal stress reduction.
subject with the dramatic physical demands of the exercise
The responses of plasma glucose and lactate to EX were
session Cortitrol supplementation diminished the
consistent between conditions. Dramatic increases in plasma
magnitude of the anticipatory response and reduced cortisol
lactate ( N15 mmol/L) demonstrated the extreme metabolic
concentrations into early recovery. These subtle effects
stress response to the exercise challenge Bush et al
implicate a physiological mechanism that does not disrupt
has shown that high force exercise produces large
cortisol’s important hormonal feedback roles in response to,
lactate and epinephrine responses, which in part stimulate
and recovery from, exercise (eg, glucose metabolism).
further release of cortisol. Lactate is correlated to epineph-
The tropic hormone corticotropin demonstrated no
rine responses after exercise stress however, Cortitrol
significant differences in the stimulatory signals to ste-
had no impact on metabolic responses (Our data
roidogenesis during REST. Pulsatility of corticotropin may
suggest the mechanism of Cortitrol is related to the adrenal
exert a major trophic effect but we did not measure
corticotropin pulsatility in this study. Owing to this
Resistance exercise has been classically shown to
limitation we calculated AUC to act as a composite
increase hypothalamic-pituitary gonadal hormones
W.J. Kraemer et al. / Metabolism Clinical and Experimental 54 (2005) 657 – 668
In general, no significant changes in androgen concentra-
a nutritional supplement. This investigation also opens the
tions were between Cortitrol and placebo con-
door to many avenues of future research.
ditions (see Table 3). However, significantly lower cortisolvalues resulted in reduced cortisol/DHEA and increased
testosterone/cortisol ratio, which would indicate a ganabolic environment during these time points [40].
This study was funded in part by a grant from
Reduced cortisol/DHEA ratio has been observed previously
Pharmanex, an NSE Company, Provo, Utah.
in marathon runners supplementing with b-sitosterol beforethe competition. This was associated with decreasedinflammatory response and cortisol concentrations during
the marathon recovery period In our study, the impact
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